Analysis of Tryptophan and Its Main Metabolite Kynurenine and the Risk of Multiple Cancers Based on the Bidirectional Mendelian Randomization Analysis

Li, Ran; Wang, Xuanyang; Zhang, Yuntao; Xu, Xiaoqing; Wang, Lulu; Wei, Chunbo; Liu, Lin; Wang, Ziqi; Liu, Ying

doi:10.3389/fonc.2022.852718

Cited by 3 publications

(4 citation statements)

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“…Tryptophan can be enzymatically hydrolyzed into kynurenine in vivo , through which to participate in cancer immune regulation ( 25 ). Our result showed that kynurenine level was downregulated in the DLC group than those of DLB and DM, while Yuzo Suzuki ( 26 ) has reported that kynurenine concentrations were significantly higher in lung cancer patients compared with the controls. Recently, Ran Li concluded that no causal relationship was found between kynurenine and lung cancers ( 27 ).…”

Section: Discussionmentioning

confidence: 48%

Decreased IGF-1 level is associated with restrained amino acid metabolism in NSCLC with diabetes mellitus

Zhang²,

Liang³

et al. 2022

Front. Endocrinol.

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The discovery of a large number of small pulmonary nodules and early diagnosis of lung cancer in the diabetic patients prompt us to re-examine the relationship between diabetes and the occurrence and development of lung cancer. The aim of this study was to explore the underlying metabolites changes in diabetes with NSCLC or benign nodule patients, and further to investigate the association of serum IGF-1 level and differentially expressed metabolites (DEMs). An untargeted metabolomics method was used to detect the changes of metabolism in diabetic patients with NSCLC on the platform of HR-MS. Serum level of IGF-1 was measured by ELISA. The patients were divided to three groups, DM, DLB (nodule), and DLC (cancer). we have identified numerous DEMs, which include amino acid, choline, and fatty acid derivatives. Further analysis of the involved metabolic pathways suggested that linoleate metabolism, tryptophan metabolism, histidine metabolism, putative anti-Inflammatory metabolites formation from EPA, and arachidonic acid metabolism were considered to be the most significant metabolic pathways between groups. Networks analysis suggested that a series of metabolites were associated with serum IGF-1among the three groups, which can be divided into 6 categories. Nine metabolites have been identified as the main DEMs among the DLC, DLB, and DM groups. In conclusion, metabolomics is a powerful and promising tool for the cancer risk evaluation in diabetic patients. Our results suggest that decreased IGF-1 level is associated with restrained amino acid metabolism in NSCLC with diabetes mellitus.

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Section: Discussionmentioning

confidence: 48%

Decreased IGF-1 level is associated with restrained amino acid metabolism in NSCLC with diabetes mellitus

Zhang²,

Liang³

et al. 2022

Front. Endocrinol.

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“…There are several reports on various cancers including liver cancer and the changes of tryptophan and its metabolites, but no consistent conclusions have been reached. 35,36 The main strengths of our study are its prospective design and the measurement of melatonin using liquid chromatography-tandem In conclusion, this prospective study observed that higher melatonin intake was significantly associated with a decreased risk of Abbreviations: HR, hazard ratio; T1-T3, the tertile groups of energy-adjusted melatonin intake. a Melatonin intake adjusted for total energy intake by Willett method.…”

Section: Discussionmentioning

confidence: 89%

“…Since tryptophan has other metabolic pathways, such as the kynurenine and indole pathways, other metabolites might have influenced the observed associations. There are several reports on various cancers including liver cancer and the changes of tryptophan and its metabolites, but no consistent conclusions have been reached 35,36 …”

Section: Discussionmentioning

confidence: 99%

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Dietary melatonin and liver cancer incidence in Japan: From the Takayama study

Wada,

Hattori,

Maruyama

et al. 2024

Cancer Science

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There is some biological plausibility that exogenous melatonin plays a role in preventing liver carcinogenesis. There has been little research on the association between melatonin intake in a normal diet and health outcomes. We evaluated the association between dietary melatonin intake and the incidence of liver cancer in a population‐based prospective study in Japan. This study included 30,824 residents of Takayama city who were 35 years of age or older in 1992 and had participated in the Takayama study, Japan. Dietary intake was assessed using a validated food frequency questionnaire at the baseline. Melatonin content in foods was measured by liquid chromatography–tandem mass spectrometry. Cancer incidence was confirmed through regional population‐based cancer registries in Gifu. Liver cancer was defined as code C22 according to the International Classification of Diseases and Related Health Problems, 10th Revision. Hazard ratios for liver cancer were estimated for the tertile groups of melatonin intake using a Cox proportional hazards model. During the mean follow‐up period of 13.6 years, 189 individuals developed liver cancer. Compared with subjects in the lowest tertile of melatonin intake, those in the middle and highest tertiles had decreased risks of liver cancer, with a significant linear trend after multivariate adjustments (hazard ratios: 0.64 and 0.65, respectively, trend p = 0.023). There was no significant interaction by sex (interaction p = 0.54). This initial finding, which needs to be confirmed by further studies, suggests that consuming melatonin‐containing foods might play a role in the prevention of liver cancer.

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Risk factors for prostate cancer: An umbrella review of prospective observational studies and mendelian randomization analyses

Cui,

Zhang,

Zhang

et al. 2024

PLoS Med

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Background The incidence of prostate cancer is increasing in older males globally. Age, ethnicity, and family history are identified as the well-known risk factors for prostate cancer, but few modifiable factors have been firmly established. The objective of this study was to identify and evaluate various factors modifying the risk of prostate cancer reported in meta-analyses of prospective observational studies and mendelian randomization (MR) analyses. Methods and findings We searched PubMed, Embase, and Web of Science from the inception to January 10, 2022, updated on September 9, 2023, to identify meta-analyses and MR studies on prostate cancer. Eligibility criteria for meta-analyses were (1) meta-analyses including prospective observational studies or studies that declared outcome-free at baseline; (2) evaluating the factors of any category associated with prostate cancer incidence; and (3) providing effect estimates for further data synthesis. Similar criteria were applied to MR studies. Meta-analysis was repeated using the random-effects inverse-variance model with DerSimonian—Laird method. Quality assessment was then conducted for included meta-analyses using AMSTAR-2 tool and for MR studies using STROBE-MR and assumption evaluation. Subsequent evidence grading criteria for significant associations in meta-analyses contained sample size, P values and 95% confidence intervals, 95% prediction intervals, heterogeneity, and publication bias, assigning 4 evidence grades (convincing, highly suggestive, suggestive, or weak). Significant associations in MR studies were graded as robust, probable, suggestive, or insufficient considering P values and concordance of effect directions. Finally, 92 selected from 411 meta-analyses and 64 selected from 118 MR studies were included after excluding the overlapping and outdated studies which were published earlier and contained fewer participants or fewer instrument variables for the same exposure. In total, 123 observational associations (45 significant and 78 null) and 145 causal associations (55 significant and 90 null) were categorized into lifestyle; diet and nutrition; anthropometric indices; biomarkers; clinical variables, diseases, and treatments; and environmental factors. Concerning evidence grading on significant associations, there were 5 highly suggestive, 36 suggestive, and 4 weak associations in meta-analyses, and 10 robust, 24 probable, 4 suggestive, and 17 insufficient causal associations in MR studies. Twenty-six overlapping factors between meta-analyses and MR studies were identified, with consistent significant effects found for physical activity (PA) (occupational PA in meta: OR = 0.87, 95% CI: 0.80, 0.94; accelerator-measured PA in MR: OR = 0.49, 95% CI: 0.33, 0.72), height (meta: OR = 1.09, 95% CI: 1.06, 1.12; MR: OR = 1.07, 95% CI: 1.01, 1.15, for aggressive prostate cancer), and smoking (current smoking in meta: OR = 0.74, 95% CI: 0.68, 0.80; smoking initiation in MR: OR = 0.91, 95% CI: 0.86, 0.97). Methodological limitation is that the evidence grading criteria could be expanded by considering more indices. Conclusions In this large-scale study, we summarized the associations of various factors with prostate cancer risk and provided comparisons between observational associations by meta-analysis and genetically estimated causality by MR analyses. In the absence of convincing overlapping evidence based on the existing literature, no robust associations were identified, but some effects were observed for height, physical activity, and smoking.

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Analysis of Tryptophan and Its Main Metabolite Kynurenine and the Risk of Multiple Cancers Based on the Bidirectional Mendelian Randomization Analysis

Cited by 3 publications

References 86 publications

Decreased IGF-1 level is associated with restrained amino acid metabolism in NSCLC with diabetes mellitus

Decreased IGF-1 level is associated with restrained amino acid metabolism in NSCLC with diabetes mellitus

Dietary melatonin and liver cancer incidence in Japan: From the Takayama study

Risk factors for prostate cancer: An umbrella review of prospective observational studies and mendelian randomization analyses

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